A mammalian model system for the pathogenesis of lentiviral, especially HIV-1, infection during fetal gestation is disclosed. The model system is used in methods of testing various regimens for prophylaxis of fetal lentiviral infection. In the model system, fetal infection is established in a pregnant mammal (e.g., a rhesus monkey, Macaca mulatta or a pigtailed macaque, Macaca nemestrina by ultrasound guided inoculation of an inoculum of a lentivirus, e.g., SIV, into the amniotic fluid. The testing methods include the analysis of the effectiveness of potential immunotherapeutic and transplacental drug therapy regimens. The model will also allow testing which viral isolates are pathogenic to the developing fetus.
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